Trehalose sugar may help prevent fatty liver disease

A NATURAL sugar called trehalose may trigger a cellular housekeeping process that cleans up excess fat buildup inside liver cells, according to a study published in the journal Science Signalling. Nonalcoholic fatty liver disease (NAFLD), which affects around a quarter of the US population, is closely linked to obesity. There is no drug treatment for the disease, but weight loss can reduce the buildup of fat.
Fructose is thought to be a major contributor to the disease, and high-fructose corn syrup is used in soft drinks and many processed foods. Studies have shown that NAFLD develops as the liver strives to process dietary sugar. Dietary sugar also has a negative impact on obesity, insulin resistance, high blood pressure and other markers of metabolic syndrome.
Excess fructose is stored in the liver as triglycerides, a kind of fat that can ultimately reach toxic levels, potentially necessitating a liver transplant. Trehalose is a natural sugar that is found in plants and insects. It is approved by the Food and Drug Administration (FDA) for human consumption.
Dr. Brian J. DeBosch, PhD, a paediatric gastroenterologist, from St. Louis Children’s Hospital in Missouri, and colleagues previously found that GLUT8, a protein on the surface of liver cells, is needed for mice to develop fatty livers in response to a high-fructose diet.
Knowing that GLUT8 carries large amounts of fructose into liver cells, they wanted to find out what might block GLUT8. Trehalose was chosen, as it had been studied in relation to neurodegenerative disorders such as prion disease or amyotrophic lateral sclerosis, known as Lou Gehrig’s disease.
In mice with these disorders, trehalose appears to cause brain cells to swallow up the abnormal proteins that accumulate. The team hypothesized that the same might happen for fat buildup in liver cells. To examine this further, they fed mice a high-fructose diet plus drinking water that contained 3% trehalose. The researchers found evidence that trehalose completely blocks the development of a fatty liver.
At the end of the study, the mice had a lower body weight, and the circulating levels of cholesterol, fatty acids and triglycerides had fallen. Trehalose appears to block the transport of energy in the form of sugar into liver cells, effectively starving the cells. This triggers a process called autophagy, or self-eating, in which the cell consumes the fat that it stores.
The team describes autophagy as a kind of “house-cleaning” process, which may occur in response to the stress of too much fat or protein buildup, or a lack of energy. DeBosch believes this treatment strategy could have potential beyond neurodegenerative and metabolic diseases, and he expects to see further interest among researchers, especially regarding its hijacking of cell-signalling pathways.

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